Research will be performed to determine gene linkage relationships and the chromosome assignment and location of human genes associated with essential cellular functions and metabolic disease. Realization of a detailed human gene map can be accomplished utilizing man-rodent somatic cell hybrids growing in tissue culture as an alternative to classical Mendelian studies. Since human chromosomes are lost in man-rodent cell hybrids, gene linkages and chromosome assignments can be determined by correlating the presence or loss of human genes and chromosomes in hybrid cells. Human gene localization to regions and subregions of chromosomes will be accomplished in cell hybrids by utilizing human parental cell lines with translocated chromosomes. These altered chromosomes will provide for the subdivision of chromosomes which facilitates the detailed mapping of human genes. Human genes that are being mapped and regionally mapped include some 60 enzymes, as well as external membrane proteins, cytoplasmic proteins, viral characteristics, and nucleotide segments using cloned genes and the recombinant DNA technology. The enzymes are associated with inherited diseases including hemolytic anemias, neurodegenerative disorders and the aminoacidopathies, essential metabolic pathways, and aspects of development. The external membrane proteins, lysosomal enzymes, and viral characteristics all function as part of a structure or cellular organelle. The DNA segments for mapping will encode several hormones, RNA, and enzyme genes. Comparative mapping of the mouse will be studied to predict chromosome assignments of human genes. A linear order and detailed map of human genes will provide a better understanding of the organization of the human genome. In addition to linkage relationships useful in genetic testing, counseling, and prenatal diagnosis, this information should provide insights into control of gene expression; assembly of complex molecules, cellular organelles and structures; aspects of genetic disease; genetic relationships; chromosomal location and gene function; and the evolution of the human genome. Such knowledge will be necessary for understanding the genetic biology of man.